This invention relates to a method of assessing the concentration of an inhalational compound (e.g., an anesthetic) in the brain of a subject after administration of the compound.
Minimum Alveolar Concentration (MAC) was introduced in 1964 as a standard of assessing the depth of anesthesia. It is defined as an anesthetic concentration in the alveolar that prevents a response to a painful stimulus in 50% of subjects. Such a definition does not incorporate the time required for an anesthetic concentration in the brain to reach equilibrium with the anesthetic concentration in the alveolar. See Lin, C. Y. (1994) Anesth Intens Care 22: 362-373. Thus, the MAC standard cannot be used to accurately assess the depth of anesthesia.
Practically, most anesthesiologists determine the depth of anesthesia based on exterior symptoms in the patient, such as ocular myosis or abnormal blood pressure. However, these symptoms vary from patient to patient, and reliance on them inevitably involves subjective judgment of the anesthesiologists. Thus, other methods have been developed. For example, one method includes repeatedly administering stimuli to a patient, recording the patient""s electrical brain activity after each stimulus, and transforming the record as an indication of the depth of anesthesia. See International Patent Publication No. WO 91/19453.
There remains a need for an objective method for assessing the depth of anesthesia.
In one aspect, this invention directs to a method of assessing the concentration of an inhalational compound in the brain of a subject. Examples of such a compounds include, not limit to, anesthetics (e.g., isoflurane, haloflurane, desflurane, sevoflurane, enflurane, ether, or nitrous oxide) or non-anesthetics (e.g., carbon dioxide or nitrogen). This method includes (1) administering a gas containing an inhalational compound into a subject to fill the pulmonary functional residual capacity; (2) after having filled the functional residual capacity with the gas, measuring an inspired compound concentration (Clxe2x80x2) and an expired compound concentration (Cexe2x80x2); (3) assessing a mixed venous compound concentration (Cbxe2x80x2) based on Formula I: Cbxe2x80x2=[Clxe2x80x2(Mxe2x88x921)+Cexe2x80x2]/M, in which M is an alveolar membrane factor for the compound; and (4) assessing a compound concentration in the brain (Cb) based on Formula II: Cb=(Cexe2x80x2+Cbxe2x80x2)/2. The alveolar membrane factor M, as will be described below, is mostly a constant parameter for each inhalational compound, may slightly vary among different subjects. It can be assessed based on Formula III: M=1xe2x88x92(Ce/Cl), in which Cl and Ce are an inspired compound concentration and an expired compound concentration, respectively, measured at the time when about 90% (i.e., 85-95%) of the functional residual capacity is filled with the gas.
In another aspect, the invention features an article that includes a machine-readable medium that stores machine-executable instructions. Such instructions causes a machine to receive values representing the concentration of a compound administered in a gas into a subject to fill the pulmonary functional residual capacity. The values include an inspired compound concentration (Cixe2x80x2) and an expired compound concentration (Cexe2x80x2), wherein the inspired compound concentration (Cixe2x80x2) and the expired compound concentration (Cexe2x80x2) are measured after having filled the functional residual capacity with the gas. The instructions also cause the machine to output a representation of a compound concentration in the brain (Cb), in which the representation of the compound concentration in the brain (Cb) can be assessed by the formula Cb=(Cexe2x80x2+Cbxe2x80x2)/2, wherein Cbxe2x80x2=[Clxe2x80x2(Mxe2x88x921)+Cexe2x80x2]/M, M is a given alveolar membrane factor for the compound. Alternatively, the values further include a second inspired compound concentration (Cl) and a second expired compound concentration (Ce), in which Cl and Ce are measured at the time when about 90% of the functional residual capacity is filled with the gas. M is assessed based by the formula M=1xe2x88x92(Ce/Cl). The instructions may further cause the machine to trigger a detector to sample the compound concentration at the time when about 90% of the functional residual capacity is filled with the gas; monitor a time interval; and trigger the detector to sample the compound from an inspiration and an expiration after filling the functional residual capacity of the subject.
In still another aspect, the invention features an apparatus that includes a display and a processor. The processor can be configured to receive values representing the concentration of a compound administered in a gas into a subject to fill the pulmonary functional residual capacity. The values include an inspired compound concentration (Clxe2x80x2) and an expired compound concentration (Cexe2x80x2), wherein the inspired compound concentration (Clxe2x80x2) and the expired compound concentration (Cexe2x80x2) are obtained after having filled the functional residual capacity with the gas. The processor can be also figured to control the display to depict a representation of a compound concentration in the brain (Cb), in which the representation of the compound concentration in the brain (Cb) is assessed by the formula Cb =(Cexe2x80x2+Cbxe2x80x2)/2, wherein Cbxe2x80x2=[Clxe2x80x2(Mxe2x88x921)+Cexe2x80x2]/M, and M is an alveolar membrane factor for the compound.
Other advantages or feature of this invention will be apparent from the following detailed description thereof.